Apoptosis is the name of the stereotyped program by which cells commit suicide. It is characterized by destruction of chromatin and degradation of the DNA, usually to nucleosomal fragments, accompanied by cell shrinkage and loss of cell substance through blabbing. Apoptosis is of wide physiological and pathological significance, important in embryogenesis, control of tissue growth and the regulation of the immune system, as well as in the elimination of cells that have sustained serious damage, particularly to their genomes. The Investigators have shown that in several lines of cells exposed to a variety of apoptosis-inducing agents, apoptosis with its accompanying genome destruction is preceded by intracellular acidification, and that the genome is preserved if this acidification is prevented. They propose to investigate the mechanism of acidification in cells undergoing apoptosis, and to study a ubiquitous acid endonuclease that may be responsible for the degradation of DNA during the apoptosis program.